CA2

Chr 8AR

carbonic anhydrase 2

Carbonic anhydrase II catalyzes the reversible hydration of carbon dioxide and is essential for bone resorption by osteoclasts and fluid regulation in various tissues including the kidney and eye. Mutations cause autosomal recessive osteopetrosis with renal tubular acidosis, affecting bone density and acid-base balance. This gene is highly intolerant to loss-of-function variants (pLI nearly 1.0), indicating that complete loss of protein function is likely pathogenic.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Osteopetrosis, autosomal recessive 3, with renal tubular acidosisMIM #259730
AR
12
Active trials
1178
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.37
LOEUF
LOF
Mechanism· G2P
Clinical SummaryCA2
🧬
Gene-Disease Validity (ClinGen)
autosomal recessive osteopetrosis 3 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.37LOEUF
pLI 0.000
Z-score 0.62
OE 0.81 (0.501.37)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.36Z-score
OE missense 0.91 (0.791.06)
128 obs / 140.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.81 (0.501.37)
00.351.4
Missense OE0.91 (0.791.06)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 10 / 12.3Missense obs/exp: 128 / 140.0Syn Z: 0.43
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCA2-related osteopetrosisLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6356th %ile
GOF
0.4579th %ile
LOF
0.3452th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CA2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Healthy Adults

Safety and Efficacy of Injectable Klotho Plasmid Gene Therapy in Humans

RECRUITING
NCT07216781Phase PHASE1MinicircleStarted 2025-10-06
Injectable Plasmid Klotho Gene Therapy
HER2-negative Breast Cancer

Neoadjuvant Concomitant Modulated Electro-hyperthermia in HER2-negative Breast Cancer

ACTIVE NOT RECRUITING
NCT05889390Phase PHASE2, PHASE3Semmelweis UniversityStarted 2023-02-20
Oncotherm EHY-2030PaclitaxelCarboplatin
COPD

Respiratory Muscles in End-stage Lung Disease: Pathophysiological Processes & Clinical Consequences

NOT YET RECRUITING
NCT06935825University Medical Center GroningenStarted 2025-09-01
Crohn DiseaseInfliximab

HLADQA1*05 Genotype and the Efficacy of Treatment With Infliximab in Chinese Population Crohn's Disease

NOT YET RECRUITING
NCT05813860Phase PHASE4Sixth Affiliated Hospital, Sun Yat-sen UniversityStarted 2023-04-30
AzathioprineInfliximab
DMD-Associated Dilated Cardiomyopathy

Modulation of SERCA2a of Intra-Myocytic Calcium Trafficking in Cardiomyopathy Secondary to Duchenne Muscular Dystrophy

RECRUITING
NCT06224660Phase PHASE1Sardocor Corp.Started 2024-10-02
SRD-001
Healthy Adults

Safety and Efficacy of Klotho and Follistatin Gene Therapy

RECRUITING
NCT07285629Phase EARLY_PHASE1MinicircleStarted 2025-12-16
Follistatin and klotho gene therapy
Postmenopausal Osteoporosis

Dried Plums and Bone Health in Postmenopausal Women

ACTIVE NOT RECRUITING
NCT02822378Phase NAPenn State UniversityStarted 2016-06-01
Dried PlumCalcium supplementVitamin D supplement
Operable Breast Cancer

Randomized Controlled Trial to Assess Blockade of Voltage Gated Sodium Channels During Surgery in Operable Breast Cancer

ACTIVE NOT RECRUITING
NCT01916317Phase PHASE3Tata Memorial HospitalStarted 2011-12-12
0.5% lignocaine 60mM
Crohn Disease

Clinical, Imaging, and Endoscopic Outcomes of Children Newly Diagnosed With Crohn's Disease

RECRUITING
NCT05781152Phase PHASE4Connecticut Children's Medical CenterStarted 2023-06-10
Anti-TNF therapy
Nervous System DiseasesCardiovascular and Cerebrovascular Diseases

Association Analysis of Cardiovascular and Nervous System Diseases and Intestinal Microbiome Based on Multi-omics Big Data and Related Applications

RECRUITING
NCT06099496Tao XinStarted 2023-04-01
Inflammatory Bowel DiseasesColitis, UlcerativeCrohn Disease

Investigation of the Correlation Between Polyamine Levels and Their Key Enzymatic Activities in Association With Inflammatory Bowel Disease Progression

RECRUITING
NCT06995170Xijing HospitalStarted 2025-01-01
Crohn Disease (CD)IBD (Inflammatory Bowel Disease)IBD - Inflammatory Bowel Disease

Combining Nutritional Therapy and Anti-TNFα Treatment in Pediatric Patients With Crohn's Disease

NOT YET RECRUITING
NCT07314606Phase NAUniversity of British ColumbiaStarted 2025-12-15
IFX + mCDED
Clinical Literature
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